The influence of emotion on temporal context models.

Temporal context models (TCMs) have been influential in understanding episodic memory and its neural underpinnings. Recently, TCMs have been extended to explain emotional memory effects, one of the most clinically important findings in the field of memory research. This review covers recent advances in hypotheses for the neural representation of spatiotemporal context through the lens of TCMs, including their ability to explain the influence of emotion on episodic and temporal memory. In recent years, simplifying assumptions of "classical" TCMs - with exponential trace decay and the mechanism by which temporal context is recovered - have become increasingly clear. The review also outlines how recent advances could be incorporated into a future TCM, beyond classical assumptions, to integrate emotional modulation.

The Role of Prefrontal Ensembles in Memory Across Time: Time-Dependent Transformations of Prefrontal Memory Ensembles.

The medial prefrontal cortex (mPFC) plays a critical role in recalling recent and remote fearful memories. Modern neuroscience techniques, such as projection-specific circuit manipulation and activity-dependent labeling, have illuminated how mPFC memory ensembles are reorganized over time. This chapter discusses the implications of new findings for traditional theories of memory, such as the systems consolidation theory and theories of memory engrams. It also examines the specific contributions of mPFC subregions, like the prelimbic and infralimbic cortices, in fear memory, highlighting how their distinct connections influence memory recall. Further, it elaborates on the cellular and molecular changes within the mPFC that support memory persistence and how these are influenced by interactions with the hippocampus. Ultimately, this chapter provides insights into how lasting memories are dynamically encoded in prefrontal circuits, arguing for a key role of memory ensembles that extend beyond strict definitions of the engram.

Forward versus backward recall: Modality testing.

OBJECTIVES: One of the most frequently applied paradigms in the clinical and experimental fields for assessing working memory is the simple span task, composed of forward and backward recall conditions. However, the utility of the simple span measures and their relation to working memory modalities has yet to be elucidated. The current study aimed to address which of the span measures is more sensitive to the differentiation between forward and backward recall in the tactile, verbal, and visuo-spatial modalities, and to test if working memory modalities differ in the disparity between the two conditions. METHODS: 134 healthy young adults performed the Tactual, Digit, and Visuo-spatial Span tasks, producing Total Correct scores and Longest Sequence score measures. RESULTS: There was an interaction effect for condition and modality type, showing better performance for the forward compared to the backward recall in both measures. However, the effect size of the Longest Sequence score was significantly higher than the Total Correct score in all tasks. Furthermore, the Visuo-spatial Span exhibited a larger difference between forward and backward recall compared to the Digit and Tactual Span, whereas no difference was found between the latter two. CONCLUSIONS: Forward and backward recall are distinguished in all three modalities, and the Longest Sequence score is more sensitive to differentiate between storage and manipulation components of working memory than the Total Correct score. Additionally, the cognitive demand imposed by manipulation compared to storage is the greatest in the visuo-spatial modality.

A review of the peak-end rule in mental health contexts.

The peak-end rule, a memory heuristic in which the most emotionally salient part of an experience (i.e., peak) and conclusion of an experience (i.e., end) are weighted more heavily in summary evaluations, has been understudied in mental health contexts. The recent growth of intensive longitudinal methods has provided new opportunities for examining the peak-end rule in the retrospective recall of mental health symptoms, including measures often used in measurement-based care initiatives. Additionally, principles of the peak-end rule have significant potential to be applied to exposure-based therapy procedures. Additional research is needed to better understand the contexts in which, and persons for whom, the peak-end rule presents a greater risk of bias, to ultimately improve assessment strategies and clinical care.

Exploring the relationship between marital quality and cognitive function: A systematic review.

Cognitive function is an important indicator of healthy aging as it is central to maintaining functional independence, performing job-related tasks, decision-making, and improving quality of life. Therefore, researchers seek to identify biopsychosocial factors that can help preserve cognitive function in aging individuals. One such factor is the maintenance of good quality marital relationships. Research has consistently shown that married individuals fare better in terms of both physical and psychological health compared to their unmarried counterparts. However, being married is not universally beneficial - the quality of a marriage is also important to consider. To explore the issue further, we conducted a systematic review to examine the association between marital quality and cognitive function. PubMed, PsycINFO, and Scopus were searched for eligible articles examining any measure of marital quality and any cognitive outcome from the inception of each database to January 9th, 2024. Following two levels of citation screening by two independent reviewers, we included 15 articles representing 11 unique studies. Data were synthesized narratively following the Synthesis without Meta-Analysis guidelines and a risk of bias assessment was conducted using the Joanna Briggs Institute checklist. Most articles had a low risk of bias. Although some findings suggested more positive marital quality was associated with improved cognitive function, the results were not uniformly positive; some results were inverse or null, depending upon factors such as differences in study designs and measures of marital quality or cognition. This review is the first attempt to synthesize the literature on this topic. Our findings highlight that any examination of marital status and cognition should also consider contextual factors such as marital quality.

The receiver operating characteristic curve accurately assesses imbalanced datasets.

Many problems in biology require looking for a "needle in a haystack," corresponding to a binary classification where there are a few positives within a much larger set of negatives, which is referred to as a class imbalance. The receiver operating characteristic (ROC) curve and the associated area under the curve (AUC) have been reported as ill-suited to evaluate prediction performance on imbalanced problems where there is more interest in performance on the positive minority class, while the precision-recall (PR) curve is preferable. We show via simulation and a real case study that this is a misinterpretation of the difference between the ROC and PR spaces, showing that the ROC curve is robust to class imbalance, while the PR curve is highly sensitive to class imbalance. Furthermore, we show that class imbalance cannot be easily disentangled from classifier performance measured via PR-AUC.

Application of the Japanese Verbal Learning Test to Patients With Alzheimer's Disease in the Early Stage.

INTRODUCTION: This study aimed to investigate the mechanism of memory function in the context of explicit memory in early-stage Alzheimer's disease (AD) using the short-form Japanese Verbal Learning Test (JVLT-9). METHODS: Participants were 20 patients with early-stage AD and a control group of 23 healthy older adults (normal controls: NC), each of whom was administered the JVLT-9, which is a verbal list learning task used to assess explicit memory comprehensively. Between-group differences for each score were investigated using the Mann-Whitney U test. A two-way analysis of variance (ANOVA) was performed for the number of correct recalls by group (AD/NC) × JVLT-9 task. In addition, the AD group was divided into a CDR 0.5 group and a CDR 1.0 group, and it was performed as a group (CDR 0.5/1.0) × JVLT-9 task two-way ANOVA. RESULTS: The results demonstrated that the AD group had lower immediate recall, learning rate, semantic clustering, and recognition discrimination and significantly higher intrusion errors compared to the NC group. Further, JVLT-9 recall and recognition rates were found to be lower with higher CDR (an index of dementia severity). CONCLUSION: These results are largely consistent with the features of explicit memory in AD reported in the English version, confirming the clinical utility of the JVLT-9 as a test of explicit memory function.

The impact of sleep quality on visual working memory varied with the duration of maintenance.

Objective: Sleep quality can affect the performance of visual working memory. However, the effect of sleep quality on the maintenance stage, which is the key to maintain the quality and efficiency of visual working memory representation, remains unclear. This study is the first to explore the effect of sleep quality on the maintenance of visual working memory information. Method: 60 healthy college students completed the Pittsburgh Sleep Quality Index (PSQI) and color recall task of visual working memory. A mixed experimental design of sleep quality (high or low) and delay duration (1, 4, or 6 s) was used to assess the effect of sleep quality on the maintenance phase of visual working memory. Results: The main effects of sleep quality were significant on visual working memory quantity, precision and offset indexes. Among the quantity index, the interaction between sleep quality and delay duration was also significant. This suggests that prolonging the delay time in the maintenance phase leads to difficulty in maintaining attention to the task for those with lower sleep quality, which results in poorer working memory quantitative representations. Conclusion: Increases in the delay duration of the maintenance phase in visual working memory intensify the impact of sleep quality on task performance. Our study provides evidence to reveal the relationship between sleep quality and visual working memory and offers recommendations for improving sleep quality and cognitive functioning in individuals.

The relative validity of nutrition assessment methods for estimating infant carotenoid intake differs by assessment tool, nutrient database, and milk carotenoid adjustment method.

Validated carotenoid assessment methods are needed to study infant carotenoid nutrition. This is a secondary analysis of repeated diet assessments of healthy participants collected at 4- (n = 21), 6- (n = 12), and 8- (n = 9) months of age in Houston, TX between April 2019 and June 2020. Intake was assessed with 3 assessment tools, analyzed with 3 nutrient databases, and underwent 3 adjustments to account for milk composition variability. We hypothesized that manual adjustment of milk carotenoid intake based on laboratory measurements would improve the validity of all assessment approaches and that using a database with greater coverage of infant food carotenoid compositions would improve accuracy. Generalized linear mixed models assessed associations between tool, nutrient database, age, and milk carotenoid adjustment variables with carotenoid, energy, fruit, and vegetable intakes. The effect of the number of food diary days on intake estimate precision was evaluated by testing the correlation between intake estimates derived from 1, 3, or 5, vs. 7 days. Visit age influenced energy intake estimates (p = .029), along with assessment tool (p = .020). Estimates of vegetable intake were influenced by tool (p = .009). Combined fruit and vegetable intake differed by nutrient database (p = .007). Carotenoid intake differed by age (p =<.0001), tool (p = .002), and nutrient database (p = .004). A minimum of 3 food diary days strongly correlated (rho = 0.79-1) with reference estimates across ages. Milk carotenoid adjustment was most influential in estimating 4-month olds' carotenoid intake, while nutrient database and tool were important for 6- and 8-month-olds', highlighting the dynamic nature of infant diet assessment validity across feeding stages.

The survival processing effect in episodic memory in older adults and stroke patients.

In the present study, we tested whether processing information in the context of an ancestral survival scenario enhances episodic memory performance in older adults and in stroke patients. In an online study (Experiment 1), healthy young and older adults rated words according to their relevance to an ancestral survival scenario, and subsequent free recall performance was compared to a pleasantness judgment task and a moving scenario task in a within-subject design. The typical survival processing effect was replicated: Recall rates were highest in the survival task, followed by the moving and the pleasantness judgment task. Although older adults showed overall lower recall rates, there was no evidence for differences between the age groups in the condition effects. Experiment 2 was conducted in a neurological rehabilitation clinic with a sample of patients who had suffered from a stroke within the past 5 months. On the group level, Experiment 2 revealed no significant difference in recall rates between the three conditions. However, when accounting for overall memory abilities and executive function, independently measured in standardized neuropsychological tests, patients showed a significant survival processing effect. Furthermore, only patients with high executive function scores benefitted from the scenario tasks, suggesting that intact executive function may be necessary for a mnemonic benefit. Taken together, our results support the idea that the survival processing task - a well-studied task in the field of experimental psychology - may be incorporated into a strategy to compensate for memory dysfunction.

Effectiveness of Catch-Up Vaccination Interventions Versus Standard or Usual Care Procedures in Increasing Adherence to Recommended Vaccinations Among Different Age Groups: Systematic Review and Meta-Analysis of Randomized Controlled Trials and Before-After Studies.

BACKGROUND: To address the global challenge of vaccine hesitancy, the Strategic Advisory Group of Experts on Immunization strongly promotes vaccination reminder and recall interventions. Coupled with the new opportunities presented by scientific advancements, these measures are crucial for successfully immunizing target population groups. OBJECTIVE: This systematic review and meta-analysis aims to assess the effectiveness of various interventions in increasing vaccination coverage compared with standard or usual care. The review will cover all vaccinations recommended for different age groups. METHODS: In February 2022, 2 databases were consulted, retrieving 1850 studies. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, 79 manuscripts were included after the assessment phase. These comprised 46 trials/randomized controlled trials (RCTs) and 33 before-after studies. A meta-analysis using a random-effects model was performed with STATA software (version 14.1.2). The selected outcome was the risk ratio (RR) of vaccination coverage improvement effectiveness. Additionally, meta-regression analyses were conducted for the included manuscripts. RESULTS: The analyses showed an overall efficacy of RR 1.22 (95% CI 1.19-1.26) for RCTs and RR 1.70 (95% CI 1.54-1.87) for before-after studies when considering all interventions cumulatively. Subgroup analyses identified multicomponent interventions (RR 1.58, 95% CI 1.36-1.85) and recall clinical interventions (RR 1.24, 95% CI 1.17-1.32) as the most effective in increasing vaccination coverage for RCTs. By contrast, educational interventions (RR 2.13, 95% CI 1.60-2.83) and multicomponent interventions (RR 1.61, 95% CI 1.43-1.82) achieved the highest increases for before-after studies. Meta-regression analyses indicated that the middle-aged adult population was associated with a higher increase in vaccination coverage (RCT: coefficient 0.54, 95% CI 0.12-0.95; before-after: coefficient 1.27, 95% CI 0.70-1.84). CONCLUSIONS: Community, family, and health care-based multidimensional interventions, as well as education-based catch-up strategies, effectively improve vaccination coverage. Therefore, their systematic implementation is highly relevant for targeting undervaccinated population groups. This approach aligns with national vaccination schedules and aims to eliminate or eradicate vaccine-preventable diseases.

Influence of a 2-week transcutaneous auricular vagus nerve stimulation on memory: findings from a randomized placebo controlled trial in non-clinical adults.

PURPOSE: Memory plays an essential role in daily life and is one of the first functions to deteriorate in cognitive impairment and dementia. Transcutaneous vagus nerve stimulation (tVNS) is a promising therapeutic method; however, its ability to enhance memory is underexplored, especially considering long-term stimulation. We aimed to investigate the effect of a 2-week course of auricular tVNS (taVNS) on memory in a non-clinical population. METHODS: This single-blind randomized placebo-wait-list controlled trial recruited 76 participants (30 men; mean age 48.32 years) and randomized them into four groups: early active/sham taVNS and late active/sham taVNS. Participation in the study lasted 4 weeks; early groups underwent 2 weeks intervention immediately following the first study site visit (days 0-13) and late groups 2 weeks after the first study site visit (days 14-27). Active and sham taVNS included 2 weeks of daily 4-h neurostimulation at the tragus or earlobe, respectively. To assess memory, we used the Rey Auditory Verbal Learning Test. RESULTS: Two weeks of active taVNS, but not sham taVNS, improved immediate recall and short-term memory score both in early and late groups. Furthermore, the improvements persisted over subsequent follow-up in early active taVNS. Importantly, the effect of active taVNS was superior to sham for immediate recall in both early and late groups. There were no statistical differences in delayed recall. CONCLUSION: Our findings suggest that taVNS has potential to improve memory, particularly immediate recall, and may be an effective method in preventing memory loss and mitigating cognitive aging.

Exercise and Fear and Safety Learning.

Fear conditioning paradigms have been studied for over 100 years and are of great interest to the behavioral and clinical sciences given that several safety learning processes (e.g., extinction learning and recall) are thought to be fundamental to the success of exposure-based therapies for anxiety and related disorders. This chapter provides an overview of preclinical and clinical investigations that examined the effects of exercise on initial fear acquisition, fear extinction learning and consolidation, and return of fear outcomes. This chapter highlights the collective body of evidence suggesting that exercise administered after extinction learning enhances the consolidation and subsequent recall of extinction memories to a greater extent than exercise administered prior to extinction learning. This suggests that the addition of exercise after exposure therapy sessions may improve treatment outcomes for people with anxiety and related disorders. Potential mechanisms are discussed in addition to suggestions for future research to improve our understanding of the effects of exercise on fear conditioning and extinction outcomes.

Lattice radiotherapy in inflammatory breast cancer: report of a first case treated with curative aim.

Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer characterized by poor prognosis. The treatment requires a multidisciplinary approach, with neoadjuvant chemotherapy, surgery, and radiation therapy (RT). Particularly, high doses of conventional RT have been historically delivered in the adjuvant setting after chemotherapy and mastectomy or as radical treatment in patients ineligible for surgery. Here, we report the case of a 49-year-old woman patient with IBC unsuitable for surgery and treated with a combination of lattice RT and fractionated external beam RT concurrent with trastuzumab, with a curative aim. One year after RT, the patient showed a complete response and tolerable toxicities. This is the first reported case of a not-operable IBC patient treated with this particular kind of RT.

The Role of ArtificiaI Intelligence in Brain Tumor Diagnosis: An Evaluation of a Machine Learning Model.

This research study explores of the effectiveness of a machine learning image classification model in the accurate identification of various types of brain tumors. The types of tumors under consideration in this study are gliomas, meningiomas, and pituitary tumors. These are some of the most common types of brain tumors and pose significant challenges in terms of accurate diagnosis and treatment. The machine learning model that is the focus of this study is built on the Google Teachable Machine platform (Alphabet Inc., Mountain View, CA). The Google Teachable Machine is a machine learning image classification platform that is built from Tensorflow, a popular open-source platform for machine learning. The Google Teachable Machine model was specifically evaluated for its ability to differentiate between normal brains and the aforementioned types of tumors in MRI images. MRI images are a common tool in the diagnosis of brain tumors, but the challenge lies in the accurate classification of the tumors. This is where the machine learning model comes into play. The model is trained to recognize patterns in the MRI images that correspond to the different types of tumors. The performance of the machine learning model was assessed using several metrics. These include precision, recall, and F1 score. These metrics were generated from a confusion matrix analysis and performance graphs. A confusion matrix is a table that is often used to describe the performance of a classification model. Precision is a measure of the model's ability to correctly identify positive instances among all instances it identified as positive. Recall, on the other hand, measures the model's ability to correctly identify positive instances among all actual positive instances. The F1 score is a measure that combines precision and recall providing a single metric for model performance. The results of the study were promising. The Google Teachable Machine model demonstrated high performance, with accuracy, precision, recall, and F1 scores ranging between 0.84 and 1.00. This suggests that the model is highly effective in accurately classifying the different types of brain tumors. This study provides insights into the potential of machine learning models in the accurate classification of brain tumors. The findings of this study lay the groundwork for further research in this area and have implications for the diagnosis and treatment of brain tumors. The study also highlights the potential of machine learning in enhancing the field of medical imaging and diagnosis. With the increasing complexity and volume of medical data, machine learning models like the one evaluated in this study could play a crucial role in improving the accuracy and efficiency of diagnoses. Furthermore, the study underscores the importance of continued research and development in this field to further refine these models and overcome any potential limitations or challenges. Overall, the study contributes to the field of medical imaging and machine learning and sets the stage for future research and advancements in this area.

Mutagenic Azido Impurities in Drug Substances: A Perspective.

Contamination of drug products and substances containing impurities is a significant concern in the pharmaceutical industry because it may impact the quality and safety of medicinal products. Special attention is required when mutagenic impurities are present in pharmaceuticals, as they may pose a risk of carcinogenicity to humans. Therefore, controlling potential mutagenic impurities in active pharmaceutical ingredients to an acceptable safety limit is mandatory to ensure patient safety. As per the International Council for Harmonization (ICH) M7 (R2)3 Guideline, mutagenic impurities are those compounds or materials that induce point mutations. In 2018, the sartan class of drugs was recalled due to the presence of N-nitrosamine impurities, which are potential mutagens. In addition to the primary impurities being detected, this class of products, especially losartan, irbesartan and valsartan, have been identified as having organic azido contaminants, which are again highly reactive toward DNA, leading to an increased risk of cancer. These azido impurities form during the preparation of the tetrazole moiety via the reaction of a nitrile intermediate with sodium azide. Given that this is a newly raised issue in the pharmaceutical world, it should be noteworthy to review the related literature. Thus, this review article critically accounts for (i) the toxicity of azido impurities and the proposed mechanism of mutagenicity, (ii) the regulatory perspective, and (iii) the sources and control strategies used during the preparation of drug substances and (iv) future perspectives.

A four-year assessment of the characteristics of Rwandan FDA drug recalls.

BACKGROUND: A drug recall is an act of removing products from the market and/or returning them to the manufacturer for disposal or correction when they violate safety laws. Action can be initiated by the manufacturing company or by the order of a regulatory body. This study aimed to assess the characteristics of Rwanda FDA drug recall and determine the association between classes of recall and recall characteristics. METHODOLOGY: This was a retrospective descriptive cross-sectional study. Data about recalled drugs were collected from the official website of the Rwanda FDA in the section assigned to "Safety alerts". The search included data reported between February 2019 and February 2023 covering four years. Data cleaning was conducted in Microsoft Excel to address missing data and inconsistencies, followed by importation into STATA/SE software version 17.0 for further cleaning and subsequent analysis. Descriptive statistics were computed for independent variables. Categorical variables were described in terms of counts and relative frequencies. Bivariate analyses used Pearson's chi-square test to illustrate the associations between categorical independent variables and recall classes. RESULTS: The study revealed that a large proportion (33.0%) of the recalled products belonged to Class I. Antibiotics constituted 35.8% of the recalled products, with contamination emerging as a leading cause and responsible for 26.4% of the recalls. India was the leading manufacturing country for the recalled products (29.2%), followed by France (17.9%), China (17.0%), Kenya (13.2%), and Russia (6.6%). An association was found between the class of recall and several recall characteristics, including the year of recall, drug category, safety issues, reporter, and manufacturing country. CONCLUSION: This study provides a comprehensive overview of the characteristics of drug recalls in Rwanda. The insights gained contribute to a nuanced understanding of recall dynamics and provide evidence-based strategies to enhance drug quality, safety, efficacy, regulatory compliance, and patient welfare.

If Engrams Are the Answer, What Is the Question?

Engram labelling and manipulation methodologies are now a staple of contemporary neuroscientific practice, giving the impression that the physical basis of engrams has been discovered. Despite enormous progress, engrams have not been clearly identified, and it is unclear what they should look like. There is an epistemic bias in engram neuroscience toward characterizing biological changes while neglecting the development of theory. However, the tools of engram biology are exciting precisely because they are not just an incremental step forward in understanding the mechanisms of plasticity and learning but because they can be leveraged to inform theory on one of the fundamental mysteries in neuroscience-how and in what format the brain stores information. We do not propose such a theory here, as we first require an appreciation for what is lacking. We outline a selection of issues in four sections from theoretical biology and philosophy that engram biology and systems neuroscience generally should engage with in order to construct useful future theoretical frameworks. Specifically, what is it that engrams are supposed to explain? How do the different building blocks of the brain-wide engram come together? What exactly are these component parts? And what information do they carry, if they carry anything at all? Asking these questions is not purely the privilege of philosophy but a key to informing scientific hypotheses that make the most of the experimental tools at our disposal. The risk for not engaging with these issues is high. Without a theory of what engrams are, what they do, and the wider computational processes they fit into, we may never know when they have been found.

Sex-Specific Differences in Serum Kallikrein-8 (KLK8): An Exploratory Study.

Background: There are indications for sex-specific differences regarding the association between kallikrein-8 (KLK8) and cognitive impairment in early stages of Alzheimer's disease for which KLK8 may be an early blood-based biomarker. These may be due to different levels of sex hormones. To correctly interpret KLK8 blood concentrations, sex-specific analyses are needed. Objective: The aim of our exploratory study was to investigate sex-specific differences in blood-based KLK8 in participants of the population-based Heinz Nixdorf Recall study with different cognitive status and the association between KLK8 and sex hormones. Methods: In 290 participants (45% women, 69.7±7.4 years (mean±SD)) we investigated sex-specific serum KLK8 differences between cognitively unimpaired (CU, 43%) and cognitively impaired (CI) participants and the association between KLK8 and dehydroepiandrosteronsulfate (DHEAS), estradiol and testosterone, using adjusted multiple linear regression. Results: The mean±SD KLK8 was similar for CU men (808.1±729.6 pg/ml) and women (795.9±577.7 pg/ml); adjusted mean-difference [95%-CI]: -95.3 [-324.1;133.5] pg/ml. KLK8 was lower in CI women (783.5±498.7 pg/ml) than men (1048.4±829 pg/ml); -261 [-493.1; -29] pg/ml. In men but not women, there was a weak indication for a positive slope between estradiol (11.9 [-0.4;24.3] pg/ml) and DHEAS (1.4 [-0.5;3.3] pg/ml) with KLK8, while testosterone had no impact. Conclusions: The results suggested a different role for KLK8 in the development of cognitive impairment in men and women, potentially influenced by sex hormones. To use blood KLK8 as an early biomarker, further research on hormonal regulation of KLK8 expression is needed as a part of the investigation of the KLK8 involvement in cognitive impairment and Alzheimer's disease pathology.